1. Field of the Invention
The present invention relates to a treatment of ocular hypertension with a synergistic combination comprising (a) a 15-ketoprostaglandin compound and (b) a carbonate dehydratase inhibitor. Said combination is characterized by an improved effect and a reduced side-effect.
The compounds used as the component (a) in the present invention are prostaglandin analogues which can be obtained synthetically.
2. Information of Prior Art
Prostaglandins (hereinafter, prostaglandins are referred to as PGs) are members of a class of organic carboxylic acid that are contained in human and most other mammalian tissues or organs and that exhibit a wide range of physiological activities. Naturally occurring PGs possess as a common structural feature the prostanoic acid skeleton: ##STR1## Some synthetic analogues have somewhat modified skeletons. The primary PGs are classified based on the structural feature of the five-membered cycle moiety into PGAs, PGBs, PGCs, PGDs, PGEs, PGFs, PGGs, PGHs, PGIs and PGJs, and also on the presence or absence of unsaturation and oxidation in the chain moiety as:
______________________________________ Subscript 1 13,14-unsaturated-15-OH Subscript 2 5,6- and 13,14-diunsaturated- 15-OH Subscript 3 5,6- 13,14- and 17,18- triunsaturated-15-OH ______________________________________
Further, PGFs are sub-classified according to the configuration of hydroxy group at position 9 into .alpha.(hydroxy group being in the alpha configuration) and .beta.(hydroxy group being in the beta configuration).
The fact that the above compounds under item (a) have ocular hypotensive activity has been known by Japanese Patent Publication No. A-108/1990 and No. A-96528/1990. The carbonate dehydratase inhibitor referred to under item (b) refers to the agents capable of specifically inhibiting enzymes which take part in the reversible reaction forming carbonate from carbon dioxide and water in living organisms, and is known to have pharmacological activities such as ocular hypotension. It has also been described in Japanese Patent Publication A-313728/1988 that prostaglandins can be coadministered with an adrenergic blocker. Such description, however, neither show a combined use of the carbonate dehydratase inhibitor and the component (a) in the present invention nor suggest that said combined use may cause synergistic increase in effect or decrease in side-effect because the adrenergic blockers are agents which inhibit the binding of the adrenergic agents with the adrenergic receptors thus exerting their pharmacological activity.
After an extensive study on the possibility that the effect of the component. (a) in the present invention is improved by combining it with a variety of compounds, the present inventor has surprisingly discovered that the effect of the component (a) is significantly improved and side-effect is decreased by co-administration with a carbonate dehydratase inhibitor such as acetazolamide. Said discovery leads to the present invention.